tbuckley/cabot-search huggingface dataset:
Albumin-Bilirubin Grade Analyses of Atezolizumab Plus Bevacizumab vs Sorafenib in Patients With Unresectable Hepatocellular Carcinoma: A Post Hoc Analysis of the Phase III IMbrave150 Study
Authors: Masatoshi Kudo, Richard S. Finn, Ann-Lii Cheng, Andrew X. Zhu, Michel Ducreux, Peter R. Galle, Naoya Sakamoto, Naoya Kato, Michitaka Nakano, Jing Jia, Arndt Vogel
Journal: Liver Cancer (2023)

Atezolizumab + bevacizumab showed survival benefit in patients with unresectable hepatocellular carcinoma (HCC) versus sorafenib in the Phase III IMbrave150 study. This exploratory analysis examined the prognostic impact of a baseline albumin-bilirubin (ALBI) score.Patients with treatment-naïve unresectable HCC, ≥1 measurable untreated lesion, and Child-Pugh class A liver function were randomized 2:1 to receive atezolizumab 1,200 mg + bevacizumab 15 mg/kg every 3 weeks or sorafenib 400 mg twice daily. Overall survival (OS) and progression-free survival (PFS) were assessed in the intention-to-treat population by ALBI/modified (m)ALBI grade. Time to deterioration (TTD; defined as time to 0.5-point increase from the baseline ALBI score over 2 visits or death) of liver function and safety were investigated.Of 501 enrolled patients, 336 were randomized to receive atezolizumab + bevacizumab (ALBI grade [G] 1: n = 191; G2: n = 144 [mALBI G2a: n = 72, G2b: n = 72]; missing ALBI grade: n = 1) and 165 to sorafenib (ALBI G1: n = 87; G2: n = 78 [mALBI G2a: n = 37; G2b: n = 41]). Median follow-up was 15.6 months. OS and PFS improved with atezolizumab + bevacizumab versus sorafenib in patients with ALBI G1 (OS HR: 0.50 [95% CI: 0.35, 0.72]; PFS HR: 0.61 [95% CI: 0.45, 0.82]). In patients with ALBI G2 or mALBI G2a or G2b, PFS was numerically longer with atezolizumab + bevacizumab versus sorafenib, but no OS benefit was seen. Median TTD in the intention-to-treat population was 10.2 months (95% CI: 8.0, 11.0) with atezolizumab + bevacizumab versus 8.6 months (95% CI: 6.2, 11.8) with sorafenib (HR: 0.82 [95% CI: 0.65, 1.03]). Safety profiles of atezolizumab and bevacizumab were consistent with previous analyses, regardless of ALBI grade.ALBI grade appeared to be prognostic for outcomes with both atezolizumab + bevacizumab and sorafenib treatment in patients with HCC. Atezolizumab + bevacizumab preserved liver function for a numerically longer duration than sorafenib.
<i>Mycobacterium abscessus</i> Cluster in Cardiac Surgery Patients Potentially Attributable to a Commercial Water Purification System
Authors: Michael Klompas, Chidiebere Akusobi, Jon Boyer, Ann Woolley, Ian D. Wolf, Robert Tucker, Chanu Rhee, Karen Fiumara, Madelyn Pearson, Charles A. Morris, Eric Rubin, Meghan A. Baker
Journal: Annals of Internal Medicine (2023)

Nontuberculous mycobacteria are water-avid pathogens that are associated with nosocomial infections. To describe the analysis and mitigation of a cluster of Mycobacterium abscessus infections in cardiac surgery patients. Descriptive study. Brigham and Women's Hospital, Boston, Massachusetts. Four cardiac surgery patients. Commonalities among cases were sought, potential sources were cultured, patient and environmental specimens were sequenced, and possible sources were abated. Description of the cluster, investigation, and mitigation. Whole-genome sequencing confirmed homology among clinical isolates. Patients were admitted during different periods to different rooms but on the same floor. There were no common operating rooms, ventilators, heater-cooler devices, or dialysis machines. Environmental cultures were notable for heavy mycobacterial growth in ice and water machines on the cluster unit but little or no growth in ice and water machines in the hospital's other 2 inpatient towers or in shower and sink faucet water in any of the hospital's 3 inpatient towers. Whole-genome sequencing confirmed the presence of a genetically identical element in ice and water machine and patient specimens. Investigation of the plumbing system revealed a commercial water purifier with charcoal filters and an ultraviolet irradiation unit leading to the ice and water machines in the cluster tower but not the hospital's other inpatient towers. Chlorine was present at normal levels in municipal source water but was undetectable downstream from the purification unit. There were no further cases after high-risk patients were switched to sterile and distilled water, ice and water machine maintenance was intensified, and the commercial purification system was decommissioned. Transmission pathways were not clearly characterized. Well-intentioned efforts to modify water management systems may inadvertently increase infection risk for vulnerable patients. National Institutes of Health.
In AF, underdosing of DOACs was not linked to reduced bleeding
Authors: Andrew Dunn
Journal: Annals of Internal Medicine (2023)

Source Citation Caso V, de Groot JR, Sanmartin Fernandez M, et al. Outcomes and drivers of inappropriate dosing of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation: a systematic review and meta-analysis. Heart. 2023;109:178-85. 36316100
Prevention of non-ventilator-associated hospital-acquired pneumonia in Switzerland: a type 2 hybrid effectiveness–implementation trial
Authors: Aline Wolfensberger, Lauren Clack, Stefanie von Felten, Mirjam Faes Hesse, Dirk Saleschus, Marie-Theres Meier, Katharina Kusejko, Roger Kouyos, Leonhard Held, Hugo Sax
Journal: The Lancet Infectious Diseases (2023)
Hospitalisations for cardiovascular and respiratory disease among older adults living near unconventional natural gas development: a difference-in-differences analysis
Authors: Kevin S Trickey, Zihan Chen, Prachi Sanghavi
Journal: The Lancet Planetary Health (2023)

BackgroundDuring 2008–15, the Marcellus shale region of the US state of Pennsylvania experienced a boom in unconventional natural gas development (UNGD) or "fracking". However, despite much public debate, little is known about the effects of UNGD on population health in local communities. Among other mechanisms, air pollution from UNGD might affect individuals living nearby through cardiovascular or respiratory disease, and older adults could be particularly susceptible.MethodsTo study the health impacts of Pennsylvania's fracking boom, we exploited the ban on UNGD in neighbouring New York state. Using 2002–15 Medicare claims, we conducted difference-in-differences analyses over multiple timepoints to estimate the risk of living near UNGD for hospitalisation with acute myocardial infarction (AMI), chronic obstructive pulmonary disease (COPD) and bronchiectasis, heart failure, ischaemic heart disease, and stroke among older adults (aged ≥65 years).FindingsPennsylvania ZIP codes that started UNGD in 2008–10 were associated with more hospitalisations for cardiovascular diseases in 2012–15 than would be expected in the absence of UNGD. Specifically, in 2015, we estimated an additional 11·8, 21·6, and 20·4 hospitalisations for AMI, heart failure, and ischaemic heart disease, respectively, per 1000 Medicare beneficiaries. Hospitalisations increased even as UNGD growth slowed. Results were robust in sensitivity analyses.InterpretationOlder adults living near UNGD could be at high risk of poor cardiovascular outcomes. Mitigation policies for existing UNGD might be needed to address current and future health risks. Future consideration of UNGD should prioritise local population health.FundingUniversity of Chicago and Argonne National Laboratories.
Learning to treat the climate emergency together: social tipping interventions by the health community
Authors: Courtney Howard, Andrea J MacNeill, Fintan Hughes, Lujain Alqodmani, Kate Charlesworth, Roberto de Almeida, Roger Harris, Bruno Jochum, Edward Maibach, Lwando Maki, Forbes McGain, Jeni Miller, Monica Nirmala, David Pencheon, Scott Robertson, Jodi D Sherman, Joe Vipond, Hao Yin, Hugh Montgomery
Journal: The Lancet Planetary Health (2023)

Accelerating the decarbonisation of local and national economies is a profound public health imperative. As trusted voices within communities around the world, health professionals and health organisations have enormous potential to influence the social and policy landscape in support of decarbonisation. We assembled a multidisciplinary, gender-balanced group of experts from six continents to develop a framework for maximising the social and policy influence of the health community on decarbonisation at the micro levels, meso levels, and macro levels of society. We identify practical, learning-by-doing approaches and networks to implement this strategic framework. Collectively, the actions of health-care workers can shift practice, finance, and power in ways that can transform the public narrative and influence investment, activate socioeconomic tipping points, and catalyse the rapid decarbonisation needed to protect health and health systems.
Estimated micronutrient shortfalls of the EAT–Lancet planetary health diet
Authors: Ty Beal, Flaminia Ortenzi, Jessica Fanzo
Journal: The Lancet Planetary Health (2023)

Unhealthy diets are a major contributor to the global burden of disease, and food systems cause substantial environmental destruction. To lay out how to achieve healthy diets for all, within planetary boundaries, the landmark EAT-Lancet Commission proposed the planetary health diet, which includes a range of possible intakes by food group and substantially restricts the intake of highly processed foods and animal source foods globally. However, concerns have been raised about the extent to which the diet provides adequate essential micronutrients, particularly those generally found in higher quantities and in more bioavailable forms in animal source foods. To address these concerns, we matched each food group point estimate within the respective range with globally representative food composition data. We then compared the resulting dietary nutrient intakes with globally harmonised recommended nutrient intakes for adults and women of reproductive age for six micronutrients that are globally scarce. To fill the dietary gaps that were estimated for vitamin B12, calcium, iron, and zinc, we suggest modifications to the original planetary health diet to achieve micronutrient adequacy (without fortification or supplementation) for adults, which included increasing the proportion of animal source foods and reducing foods high in phytate.
Rifaximin-α for liver fibrosis in patients with alcohol-related liver disease (GALA-RIF): a randomised, double-blind, placebo-controlled, phase 2 trial
Authors: Mads Israelsen, Bjørn Stæhr Madsen, Nikolaj Torp, Stine Johansen, Camilla Dalby Hansen, Sönke Detlefsen, Peter Andersen, Johanne Kragh Hansen, Katrine Prier Lindvig, Ditlev Nytoft Rasmussen, Katrine Holtz Thorhauge, Maria Kjærgaard, Morten Karsdal, Torben Hansen, Manimozhiyan Arumugam, Jonel Trebicka, Maja Thiele, Aleksander Krag, Ema Anastasiadou, Manimozhian Arumugam, Peer Bork, Torben Hansen, Roland Henrar, Hans Israelsen, Morten Karsdal, Cristina Legido-Quigley, Hans Olav Melberg, Maja Thiele, Jonel Trebicka, Aleksander Krag, Peer Bork, Mathias Mann, Jelle Matthijnssens, Aleksander Krag, Torben Hansen
Journal: The Lancet. Gastroenterology & hepatology (2023)

Alcohol is the leading cause of liver-related mortality worldwide. The gut-liver axis is considered a key driver in alcohol-related liver disease. Rifaximin-α improves gut-barrier function and reduces systemic inflammation in patients with cirrhosis. We aimed to compare the efficacy and safety of rifaximin-α with placebo in patients with alcohol-related liver disease.
Global estimates of daily ambient fine particulate matter concentrations and unequal spatiotemporal distribution of population exposure: a machine learning modelling study
Authors: Wenhua Yu, Tingting Ye, Yiwen Zhang, Rongbin Xu, Yadong Lei, Zhuying Chen, Zhengyu Yang, Yuxi Zhang, Jiangning Song, Xu Yue, Shanshan Li, Yuming Guo
Journal: The Lancet Planetary Health (2023)
Artificial intelligence-based model for lymph node metastases detection on whole slide images in bladder cancer: a retrospective, multicentre, diagnostic study
Authors: Shaoxu Wu, Guibin Hong, Abai Xu, Hong Zeng, Xulin Chen, Yun Wang, Yun Luo, Peng Wu, Cundong Liu, Ning Jiang, Qiang Dang, Cheng Yang, Bohao Liu, Runnan Shen, Zeshi Chen, Chengxiao Liao, Zhen Lin, Jin Wang, Tianxin Lin
Journal: The Lancet Oncology (2023)
The exposome and liver disease - how environmental factors affect liver health
Authors: Robert Barouki, Michel Samson, Etienne B. Blanc, Massimo Colombo, Jessica Zucman-Rossi, Konstantinos N. Lazaridis, Gary W. Miller, Xavier Coumoul
Journal: Journal of Hepatology (2023)

Since the initial development of the exposome concept, much effort has been devoted to the characterisation of the exposome through analytical, epidemiological, and toxicological/mechanistic studies. There is now an urgent need to link the exposome to human diseases and to include exposomics in the characterisation of environment-linked pathologies together with genomics and other omics. Liver diseases are particularly well suited for such studies since major functions of the liver include the detection, detoxification, and elimination of xenobiotics, as well as inflammatory responses. It is well known that several liver diseases are associated with i) addictive behaviours such as alcohol consumption, smoking, and to a certain extent dietary imbalance and obesity, ii) viral and parasitic infections, and iii) exposure to toxins and occupational chemicals. Recent studies indicate that environmental exposures are also significantly associated with liver diseases, and these include air pollution (particulate matter and volatile chemicals), contaminants such as polyaromatic hydrocarbons, bisphenol A and per-and poly-fluorinated substances, and physical stressors such as radiation. Furthermore, microbial metabolites and the "gut-liver" axis play a major role in liver diseases. Exposomics is poised to play a major role in the field of liver pathology. Methodological advances such as the exposomics-metabolomics framework, the determination of risk factors' genomic and epigenomic signatures, and cross-species biological pathway analysis should further delineate the impact of the exposome on the liver, opening the way for improved prevention, as well as the identification of new biomarkers of exposure and effects, and additional therapeutic targets.
Concurrent onset of skin and joint symptoms correlates with higher psoriatic arthritis disease activity: A single-center retrospective study
Authors: Minjia Tan, Jingjin Hu, Hui Xiao, Qiaolin Wang, Kun Hu, Xingyu Li, Jing Yang, Mi Zhang, Junchen Chen, Wu Zhu, Yehong Kuang
Journal: Journal of the American Academy of Dermatology (2023)
How Ophthalmologists Can Decarbonize Eye Care
Authors: Brooke Sherry, Samuel Lee, Maria De Los Angeles Ramos Cadena, Gregory Laynor, Sheel R. Patel, Maxine dellaBadia Simon, Eric G. Romanowski, Sarah E. Hochman, Joel S. Schuman, Christina Prescott, Cassandra L. Thiel
Journal: Ophthalmology (2023)
Primary cilia sense glutamine availability and respond via asparagine synthetase
Authors: Maria Elena Steidl, Elisa A. Nigro, Anne Kallehauge Nielsen, Roberto Pagliarini, Laura Cassina, Matteo Lampis, Christine Podrini, Marco Chiaravalli, Valeria Mannella, Gianfranco Distefano, Ming Yang, Mariam Aslanyan, Giovanna Musco, Ronald Roepman, Christian Frezza, Alessandra Boletta
Journal: Nature Metabolism (2023)

Abstract Depriving cells of nutrients triggers an energetic crisis, which is resolved by metabolic rewiring and organelle reorganization. Primary cilia are microtubule-based organelles at the cell surface, capable of integrating multiple metabolic and signalling cues, but their precise sensory function is not fully understood. Here we show that primary cilia respond to nutrient availability and adjust their length via glutamine-mediated anaplerosis facilitated by asparagine synthetase (ASNS). Nutrient deprivation causes cilia elongation, mediated by reduced mitochondrial function, ATP availability and AMPK activation independently of mTORC1. Of note, glutamine removal and replenishment is necessary and sufficient to induce ciliary elongation or retraction, respectively, under nutrient stress conditions both in vivo and in vitro by restoring mitochondrial anaplerosis via ASNS-dependent glutamate generation. Ift88-mutant cells lacking cilia show reduced glutamine-dependent mitochondrial anaplerosis during metabolic stress, due to reduced expression and activity of ASNS at the base of cilia. Our data indicate a role for cilia in responding to, and possibly sensing, cellular glutamine levels via ASNS during metabolic stress.
Elena Galea (1962–2023)
Authors: Douglas L. Feinstein
Journal: Nature Neuroscience (2023)

It was at Cornell I first met Elena, which led to life-long collaborations and a deep friendship.At that time, methods for quantifying mRNA levels were being developed, and together we devised ways to quantify astrocyte mRNAs.Elena's work on cerebral vasculature provided a smooth transition into nitric oxide (NO) research.We were fortunate that Carl Nathan, studying macrophage NO production, was at Cornell and helped us to characterize inducible NO synthase (iNOS) in astrocytes, leading to Elena's 1992 PNAS paper.That led to a series of papers describing the regulation of astrocyte iNOS expression, her cloning of the INOS (also known as NOS2) mRNA from astrocytes, and confirmation that it is expressed in astrocytes as well as microglia.Elena remained at Cornell for several years, collaborating with Eugene Golanov to examine intrinsic mechanisms underlying neurogenic protection from hypoxia and ischemia, focusing on activation of the fastigial nucleus and endothelial cell responses.Elena spent 7 years living in the upper East Side of Manhattan, attending concerts at Lincoln Center, strolling through art galleries in Greenwich village, and relaxing in Central Park.She was a connoisseur of exotic cuisine, always ready to head to an Ethiopian restaurant; and was famous for her home-made gazpacho.
Forty-hertz light stimulation does not entrain native gamma oscillations in Alzheimer’s disease model mice
Authors: Marisol Soula, Alejandro Martín-Ávila, Yiyao Zhang, Annika Dhingra, Noam Nitzan, Martin J. Sadowski, Wen-Biao Gan, György Buzsáki
Journal: Nature Neuroscience (2023)
Multiomic analyses implicate a neurodevelopmental program in the pathogenesis of cerebral arachnoid cysts
Authors: Adam J. Kundishora, Garrett Allington, Stephen McGee, Kedous Y. Mekbib, Vladimir Gainullin, Andrew T. Timberlake, Carol Nelson-Williams, Emre Kiziltug, Hannah Smith, Jack Ocken, John Shohfi, August Allocco, Phan Q. Duy, Aladine A. Elsamadicy, Weilai Dong, Shujuan Zhao, Yung-Chun Wang, Hanya M. Qureshi, Michael L. DiLuna, Shrikant Mane, Irina R. Tikhonova, Po-Ying Fu, Christopher Castaldi, Francesc López-Giráldez, James R. Knight, Charuta G. Furey, Bob S. Carter, Shozeb Haider, Andres Moreno-De-Luca, Seth L. Alper, Murat Gunel, Francisca Millan, Richard P. Lifton, Rebecca I. Torene, Sheng Chih Jin, Kristopher T. Kahle
Journal: Nature Medicine (2023)
Maximizing the GDPR potential for data transfers: first in Europe
Authors: Heidi Beate Bentzen, Hilde Kvammen Olav, Giske Ursin
Journal: The Lancet Regional Health - Europe (2023)

During the pandemic, rapid international data sharing was key to finding medical solutions.Legal derogations made some pandemic data transfers possible. 1However, non-pandemic medical research, including cancer research, follows regular legal rules, and these rules currently create data transfer stalls, delaying medical advancements. 1][4] Transfers to most of the US private sector can proceed provided appropriate safeguards are in place, but presently, US cloud providers such as Amazon Web Services, Google Cloud, and Microsoft Azure that provide large-scale, advanced data processing solutions can often not be used. 5egal challenges therefore affect clinical trials when 1) the pharmaceutical company uses a US subcontractor providing a cloud-based analysis platform, and/or 2) legally mandated information including safety data must be reported to regulatory authorities such as the US Food and Drug Administration (FDA).In the following, we describe the use of a very narrow safety valve derogation in the EU General Data Protection Regulation (GDPR) 2016/679 to enable such transfers.
B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection
Authors: Spencer T. Chen, Thiago Y. Oliveira, Anna Gazumyan, Melissa Cipolla, Michel C. Nussenzweig
Journal: Immunity (2023)

Germinal centers (GCs) are sites of B cell clonal expansion, diversification, and antibody affinity selection. This process is limited and directed by T follicular helper cells that provide helper signals to B cells that endocytose, process, and present cognate antigens in proportion to their B cell receptor (BCR) affinity. Under this model, the BCR functions as an endocytic receptor for antigen capture. How signaling through the BCR contributes to selection is not well understood. To investigate the role of BCR signaling in GC selection, we developed a tracker for antigen binding and presentation and a Bruton's tyrosine kinase drug-resistant-mutant mouse model. We showed that BCR signaling per se is necessary for the survival and priming of light zone B cells to receive T cell help. Our findings provide insight into how high-affinity antibodies are selected within GCs and are fundamental to our understanding of adaptive immunity and vaccine development.
Wearable device and smartphone data quantify ALS progression and may provide novel outcome measures
Authors: Stephen A. Johnson, Marta Karas, Katherine M. Burke, Marcin Straczkiewicz, Zoe A. Scheier, Alison P. Clark, Satoshi Iwasaki, Amir Lahav, Amrita S. Iyer, Jukka-Pekka Onnela, James D. Berry
Journal: npj Digital Medicine (2023)

Amyotrophic lateral sclerosis (ALS) therapeutic development has largely relied on staff-administered functional rating scales to determine treatment efficacy. We sought to determine if mobile applications (apps) and wearable devices can be used to quantify ALS disease progression through active (surveys) and passive (sensors) data collection. Forty ambulatory adults with ALS were followed for 6-months. The Beiwe app was used to administer the self-entry ALS functional rating scale-revised (ALSFRS-RSE) and the Rasch Overall ALS Disability Scale (ROADS) surveys every 2-4 weeks. Each participant used a wrist-worn activity monitor (ActiGraph Insight Watch) or an ankle-worn activity monitor (Modus StepWatch) continuously. Wearable device wear and app survey compliance were adequate. ALSFRS-R highly correlated with ALSFRS-RSE. Several wearable data daily physical activity measures demonstrated statistically significant change over time and associations with ALSFRS-RSE and ROADS. Active and passive digital data collection hold promise for novel ALS trial outcome measure development.
Targeting synthetic lethal paralogs in cancer
Authors: Colm J. Ryan, Ishan Mehta, Narod Kebabci, David J. Adams
Journal: Trends in cancer (2023)

Synthetic lethal interactions, where mutation of one gene renders cells sensitive to inhibition of another gene, can be exploited for the development of targeted therapeutics in cancer. Pairs of duplicate genes (paralogs) often share common functionality and hence are a potentially rich source of synthetic lethal interactions. Because the majority of human genes have paralogs, exploiting such interactions could be a widely applicable approach for targeting gene loss in cancer. Moreover, existing small-molecule drugs may exploit synthetic lethal interactions by inhibiting multiple paralogs simultaneously. Consequently, the identification of synthetic lethal interactions between paralogs could be extremely informative for drug development. Here we review approaches to identify such interactions and discuss some of the challenges of exploiting them.